Psychiatry 61

Antidepressant treatment for

depression in the elderly

There is a high risk of side effects when prescribing antidepressants in the elderly. These can
be avoided or minimised by tailoring the choice of antidepressant to the individual, by being
aware of potential drug interactions and by bearing in mind the impact of co-morbidities.
Drs Ayodeji Soyinka and David Lawley explore the evidence base and main side effects of
antidepressants in common use in the elderly and how these might influence prescribing.

DR AYODEJI SOYINKA is a Specialist Registrar in Old Age

Psychiatry and DR DAVID LAWLEY is a Consultant in Old Age
Psychiatry, Humber Mental Health Teaching NHS Trust

epression is a common symptom in later

life. The average prevalence of clinically
signicant depressive syndrome in
community dwelling older people is estimated to be
13.5 per cent1. However, the rate of strictly dened
depressive disorder in community dwelling older
people using standardised diagnostic criteria such
as the ICD 102 or DSM 43 is lower, between 0.5 and
three per cent4. The rate is higher among elderly
patients in hospitals or in nursing homes5. It is also
higher among those with chronic medical conditions
such as Parkinsons disease, cardiovascular diseases,
Chronic Obstructive Pulmonary Disease (COPD),
dementia and stroke5,6,7.
Because antidepressants are inexpensive and
readily available, they tend to be prescribed for
elderly people with depressive disorder. While it
is good practice that elderly people are given the
opportunity to benefit from what has been shown
to be effective pharmacological interventions, the
wide spread use of antidepressants can expose
elderly people to untoward effects. This is because
the elderly as a group are more prone to side
effects of medications including antidepressants8,
and they are more likely to have multiple physical
pathologies and to be taking multiple medications.
This increases their risk of drugdrug interactions
and drugdisease interactions significantly.
There may also be age related pharmacokinetic

changes affecting the absorption, protein binding,

distribution, metabolism and excretion of drugs.
Despite this, not much attention is being
paid to the adverse effects of antidepressants in
the elderly in national guidelines, research and
media attention. For instance there is only a brief
reference to the elderly in the National Institute of
Health and Clinical Excellence (NICE) guideline
on the management of depression in primary
and secondary care released in December 20049.
Elderly people over the age of 75 years are underrepresented in clinical trials of antidepressants and
as a result the evidence base for use in this group
of people is relatively poor10-12.
Since the introduction of the first
tricyclic antidepressants in the late 50s, the
psychopharmacology of antidepressants has
developed a great deal and as a result, newer
antidepressants with much improved tolerability
and side effect profiles are now in routine clinical
use. This is not to say that newer antidepressants
are free from significant side effects. For example,
gastrointestinal bleeding in elderly people can
be associated with taking Selective Serotonin
Reuptake Inhibitors (SSRIs)13. Potential side
effects can, however, be avoided or minimised
by tailoring the choice of antidepressant to the
individual, by being aware of potential drug
february 2006 / midlife and beyond / geriatric medicine

62 Psychiatry
interactions and by bearing in mind the impact
of co-morbidities. In this article, we explore the
evidence base for effectiveness and the main
side effects of antidepressants in common use
in the elderly and how both these factors might
influence prescribing.

Effectiveness
The efficacy and effectiveness of antidepressant
treatment in depressed elderly people have
been demonstrated in randomised control trials
and reviews14,15. Available data suggest that
antidepressants are effective in 50 to 60 per cent
of cases compared with a 30 per cent recovery
rate on placebo4. The placebo response is greatest
in those with mild depressive disorder and hence
antidepressants are not recommended as initial
treatment in those with mild depressive disorders.
This is consistent with the NICE guideline9.
All antidepressants have roughly equal efficacy,
although the effectiveness may differ depending
on tolerability. The general consensus is that
SSRIs and other newer antidepressants are
better tolerated than the tricyclics and related
antidepressants. In line with this, NICE
recommends that an SSRI should be first choice
when an antidepressant is to be prescribed
in routine care9. Of course, the choice of
antidepressant will depend on other factors as well
as including patients preference, co-morbidity,
potential side effects, risk of drug interactions,
past use of antidepressants and risk of overdose as
well as associated symptoms of depression such as
insomnia and agitation.
In patients severely ill with depression there
is a contention that tricyclic antidepressants are
more effective than SSRIs but the evidence is
inconclusive. Also, in some studies which were not
necessarily in older people, venlafaxine has also
been shown to be more effective than the SSRIs in
the management of moderately severe depression5.
Venlafaxine at doses above 200mg/day
is a recommended treatment option in the
management of refractory depression16. This
complies with NICE guidelines that venlafaxine
should be considered in those who have failed to
respond to two trials of antidepressants.
It is very important to be aware that older people
take longer to respond to antidepressant treatment
and as a consequence are at risk of being
prematurely considered non responsive. They may
have their antidepressant switched when they
geriatric medicine / midlife and beyond / february 2006

are yet to have an adequate trial of treatment. In

order to reduce this risk, NICE recommends that
in older adults antidepressant treatment should
be given for a minimum of six weeks before it is
considered ineffective9. In those who have shown
partial response during the first six weeks, NICE
recommends treatment for a further six weeks9.
Maintenance treatment is recommended for
those who have recovered from an episode of
depression. After the first episode, the expert
consensus on the treatment of depression in older
patients is that treatment should continue for at
least one year12.
NICE has also recommended that patients who
have experienced two or more depressive episodes
in the recent past and have experienced significant
functional impairment during these episodes
should be advised to continue treatment for two
years. This applies to both older and working age
adults. Patients should be maintained on the same
dose that led to remission.

Some common side effects of

antidepressants
This article will now explore common
antidepressant side effects that are of particular
significance in the elderly person. We will look in
detail at how side effects may arise and how it may
influence antidepressant choice.

Postural hypotension
Lowering of blood pressure is one of the most
common cardiac effects of antidepressants in
the elderly. When severe, it can result in postural
hypotension. Postural hypotension is partly due
to the blockade of alpha-1 adrenergic receptors.
The risk of postural hypotension is increased in
those with left sided heart failure and in those on
antihypertensive or diuretic treatment17.
The following antidepressants are associated
with high to moderate risk of postural hypotension
tricyclics, monoamine oxidase inhibitors,
trazodone, and nefazodone16. Lofepramine does
not lower blood pressure as much as the other
tricyclics, and although the risk is less, postural
hypotension can occur during treatment with
other antidepressants including venlafaxine,
mirtazapine and the SSRIs18. Venlafaxine can also
increase blood pressure especially at doses above
200mg daily thus blood pressure measurement
is recommended at higher doses. Postural drop

64 Psychiatry
tends to occur early in the course of treatment
and since it is not dose dependent, unless a patient
is on a high dose, dose reduction is unlikely to
be of benefit6. Postural hypotension is associated
with increased risk of falls and fractures. The risk
can be significantly reduced by checking for a
history of postural drop and by measuring standing
and supine blood pressures before prescribing
antidepressants that are associated with this side
effect, especially tricyclics. Postural hypotension
can be managed by changing to a different class of
antidepressant or, if for clinical reasons this is not
possible, fludrocortisone and pressure stockings
can be used.

Anticholinergic side effects

These include dry mouth, constipation, urinary
hesitancy, blurred vision and tachycardia.
Anticholinergic side effects are particularly
associated with the tricyclics because of their
high affinity for the muscarinic receptor. These
symptoms can have a significant impact on the
quality of life of an elderly person. Many elderly
people suffer from some degree of visual loss
that may be due to a variety of causes such as
cataract and age related macular degeneration.
Antidepressant induced blurred vision can worsen
visual loss and as a result can affect the elderly
persons ability to manage. Loss of vision also
increases the persons risk of falls and associated
complications. Tricyclics and SSRIs both produce
dry mouth as a side effect and this can make the
use of dentures more difficult. It also increases
the risk of oral infections such as candidiasis18.
It is important to bear this possibility in mind
especially in those who are already prescribed
drugs that produce xerostomia such as diuretics.
Urinary hesitancy may result in urinary retention
especially in those with prostate problems. These
complications can be prevented through careful
choice of antidepressants and monitoring.

risk of cardiovascular disease many of whom

would be elderly9. ECG changes that are clinically
significant include lengthening of the PR, QRS and
QT intervals6. Tricyclics are contraindicated after a
recent myocardial infarction18.
In December 2004, following review of the
safety of antidepressants, the Committee on
the Safety of Medicines (CSM) recommended
that venlafaxine should no longer be prescribed
for patients with heart diseases, electrolyte
imbalance or hypertension and that treatment with
venlafaxine should be initiated only by specialist
mental health practitioners including general
practitioners with a special interest in mental
health. The recommendation arose out of the
CSMs concern that venlafaxine has been linked to
incidents of sudden death and fatal overdose19. The
company that manufactures venlafaxine disagrees
with the CSM findings and they are challenging
the recommendation.
SSRIs are generally recommended in
cardiovascular diseases. Of all the SSRIs, sertraline
is the one with the best evidence in this group of
patients. In those with a history of acute myocardial
infarction or unstable angina, sertraline has been
shown to be a safe and effective antidepressant7.

Risk of overdose

Cardiac side effects

In the management of depressed people at high

risk of overdose, it is very important to avoid
antidepressants that are lethal in overdose. In view
of their cardiotoxicity, tricyclics are dangerous
in overdose and should be avoided in patients
who are suicidal. Compared with other tricyclics,
lofepramine is less cardiotoxic. As highlighted
above, venlafaxine has also been linked with
cardiotoxicity in overdose and should also be
avoided in patients who are at high risk of self
harm. An Australian study also found that the
SSRIs are relatively safe in overdose except
citalopram, which was found to be significantly
associated with QTc prolongation20.

Tricyclics have a quinidine like effect, in that they

have type 1a anti-arrhythmic properties. As a
result of this property they tend to slow cardiac
conduction and can occasionally induce heart block
and arrhythmia6. In view of this, tricyclics should
be prescribed with caution in patients with preexisting cardiovascular diseases. NICE recommends
obtaining an electrocardiogram (ECG) and
blood pressure measurement before prescribing
a tricyclic for depressed patients at significant

Similarly, in a two year retrospective review of

consecutive patients admitted to the toxicology unit
of Edinburgh Royal Infirmary, the researchers found
that in comparison to venlafaxine, mirtazapine and
nefazodone, citalopram was more likely to cause
QT prolongation21. Citalopram, therefore, should be
prescribed with caution in those who are at risk of
taking an overdose especially those with a history of
cardiovascular disease.

geriatric medicine / midlife and beyond / february 2006

Psychiatry 65
Table 1.

Doses in the elderly

Antidepressants

Starting dose
Elderly

Maximum dose

Starting dose
Adults

Maximum dose

Dosulepin
Trazodone
Citalopram
Fluoxetine

50-75mg
100mg
20mg
20mg

75mg*
300mg
40mg
60mg

75mg
150mg
20mg
20mg

150mg
300mg
60mg
80mg

* (may be sufficient)

Delirium
Delirium and confusion can be induced by
antidepressant treatment. These are mainly due to
the anticholinergic and antihistaminic effects of the
antidepressant agent hence these particular side
effects are more likely to occur in those elderly
patients taking tricyclics rather than other groups
of antidepressants. The risk is greatest in those
with an underlying dementia. Delirium can present
with affective symptoms and because of this, may
be confused with worsening of depression. It is
very important to bear this possibility in mind
especially in those patients whose depression is
worsening despite adequate treatment.

Hyponatraemia and syndrome of

inappropriate ADH secretion
All antidepressants have been implicated
in inducing hyponatraemia although it has
been reported more frequently with SSRIs.
Being elderly is a recognised risk factor for
antidepressant induced hyponatraemia. Other
risk factors include female sex, low body weight,
co-therapy with other drugs known to induce
hyponatraemia (carbamazepine, diuretics, Non
Steroidal Anti-Inflammatory Drugs (NSAIDs)
and cancer chemotherapy), medical co-morbidities
(hypothyroidism, diabetes, COPD, hypertension,
head injury, stroke, various cancers) and impaired
renal function16. The CSM has advised that
hyponatraemia should be considered in all
patients who develop drowsiness, confusion or
convulsions while taking an antidepressant18.
When mild hyponatraemia can present with
lethargy, which again could be misinterpreted
as worsening depression and in response the
antidepressant dose could be increased. This could
make the hyponatraemia worse. Management of
hyponatraemia involves stopping all offending
drugs including antidepressants22. Mild cases can
be managed by fluid restriction21 and daily

monitoring of sodium. Patients with serum sodium

less than 125mmol/l should be referred for specialist
medical care16.

Upper gastrointestinal bleed

Antidepressants have also been linked with a
variety of abnormal bleeding conditions including
gastrointestinal bleeding13, 23, 24, 25. The results of
some studies suggest that the risk of abnormal
bleeding correlates with the degree of serotonin
reuptake inhibition by the antidepressant23, 24.
The biological basis for this is that serotonin is
involved in platelet aggregation thus agents that
prevent reuptake may reduce platelet serotonin
stores and as a consequence impair platelet
function. SSRIs have been shown to increase the
risk of gastrointestinal bleed in the elderly13, 25. It is
important to consider this when prescribing SSRIs
and other serotonergic antidepressants for elderly
people. The risk of abnormal bleeding may be
higher in those over the age of 80 years, those with
previous history of gastrointestinal bleed or those
on NSAIDs and aspirin.
Mirtazapine can cause reversible
agranulocytosis. People prescribed mirtazapine
should be informed of this risk and advised
to report any fever, sore throat or other signs
of infection during treatment18. Blood count
monitoring is also recommended.

Sexual dysfunction
Sexual dysfunction such as arousal problems,
reduced libido, delayed orgasm and impaired
ejaculation are recognised side effects associated
with all classes of antidepressants. Some
antidepressants are considered to be less
likely to cause sexual dysfunction. There
is however insufficient evidence in the literature
to support this claim. One systematic review
february 2006 / midlife and beyond / geriatric medicine

66 Psychiatry
found that available evidence was insufficient to
justify claims of differences in the propensities
of antidepressants to cause sexual dysfunction26.
Sexual side effects are often not reported but it
is necessary to consider them when discussing
the risk and benefit of a particular antidepressant.
Trazodone, for example, can rarely cause
priapism.

Akathisia
Akathisia is an extrapyramidal side effect that is
most often associated with typical antipsychotic
medications but can also be caused by
antidepressants. It is characterised by difficulty
staying still and an intense feeling of inner
restlessness. There is some evidence in support of
the view that akathisia induces suicidal behaviour27.
Bearing this in mind, clinicians are advised by
NICE to actively seek out signs of akathisia
especially in the early stages of treatment.
Akathisia can be difficult to diagnose, hence
a high index of suspicion is needed. It is managed
by withdrawing the offending drug or by reducing
the dose if this is possible. Where dose reduction is
not possible, the patient can be treated with a betablocker such propranolol and if this is ineffective
then a benzodiazepine such as diazepam or
clonazepam could be used28.

Some patient characteristics of

signicance in the elderly
Agitated and anxious patients
Tricyclic antidepressants could be considered
as possible alternatives to SSRIs in situations
where sedation is required, though this must
be balanced against the risk of side effects due
to anticholinergic effects or cardiotoxicity. An
alternative approach would be to prescribe
sedatives, such as short acting benzodiazepines for
a limited period of time, as an adjunct to the SSRI.
In psychotic depression, antipsychotic drugs should
be added to the antidepressant, in order to fulfil
the dual role of sedation.

Dementia
A recent Cochrane review revealed that this
is a poorly researched area and as such there
is not much evidence supporting the efficacy
of antidepressants in people with dementia29.
geriatric medicine / midlife and beyond / february 2006

Antidepressants with strong anticholinergic

properties such as the tricyclics might worsen
confusion and are best avoided. In clinical practice,
SSRIs are usually prescribed when treating
depression in people with dementia. Where a
person with dementia has difficulty adhering to
treatment, an antidepressant with a long half
life such as fluoxetine could be prescribed as it
could be taken every other day. Furthermore,
omitting doses through forgetfulness is unlikely to
precipitate withdrawal symptoms.

Parkinsons disease
Parkinsons disease is a disease of later life, and
40 to 50 per cent of people with Parkinsons
disease will experience co-morbid depression30.
The treatment of Parkinsons disease involves
the use of combinations of drugs with potential
risk of drug interaction. Therefore, prescribing an
antidepressant for co-morbid depression could
further increase this risk. Tricyclics and SSRIs
are effective pharmacotherapy for depression in
Parkinsons disease but there are some concerns
related to side effects. Tricyclics, for instance,
may worsen cognitive function, cause orthostatic
hypotension or induce delusions30.
There is also debate that SSRIs may worsen
parkinsonism. On the positive side, tricyclics
might help extrapyramidal symptoms due to their
anticholinergic effects31. Given their favourable
side effect profiles and reduced drug interactions,
SSRIs are recommended, particularly those with
neutral or weak dopaminergic effects such as
sertraline and citalopram. SSRIs should not be
prescribed for patients on selegiline (a monoamine
oxidase-B inhibitor) because of increased risk of
serotonin syndrome18.

Dose reduction
Despite the advancement in psychopharmacology,
the adage start low and go slow is advocated
when prescribing antidepressants in elderly people.
In working age adults, most new antidepressants
can be started at their therapeutic dose without
the need for dose titration. In the elderly dose
titration is often done in an effort to reduce
the risk of side effects. When dose titration is
carried out, it is important that the therapeutic
dose is achieved where tolerable although there
are studies suggesting that elderly people may
respond to lower doses of antidepressant. For
some antidepressants, the manufacturers have

Psychiatry 67
Key points
>
>
>
>

>

Older people are at a high risk of side

effects and drug interactions.
Antidepressants used should be chosen
carefully in order to reduce this risk.
SSRIs are recommended as first line
antidepressant in routine care.
Antidepressants should be tailored to the
individual patient taking into consideration
the potential for drug interaction, the effect
of physical co-morbidity and most
importantly the patients previous history of
antidepressant use.
Older people take longer to respond and
should be treated for longer before they
are considered non responsive.

recommended a reduced initial dose and a lower

final dose in the elderly person18.

Discontinuation syndrome
Discontinuation syndrome may occur following
abrupt cessation of antidepressant treatment.
Patients often report dizziness, nausea, vomiting,
flu like symptoms, fatigue, anxiety and irritability.
These symptoms are usually self limiting but on
occasions can be severe. All patients prescribed
antidepressants must be informed of the risk of
discontinuation syndrome9.
Discontinuation syndrome is more likely
with antidepressants with short half lives, such
as paroxetine. Fluoxetine, an antidepressant with
a long half life, is recommended as a means of
managing withdrawal symptoms in those patients
who have had difficulty in stopping treatment.
Also, when an antidepressant is to be stopped, this
should be done by gradual dose reduction over a
number of weeks.

Conclusion
SSRIs are currently the drugs of first choice in
the treatment of moderate to severe depression in
the elderly because of their more favourable side
effect profiles and lower risk of drug interaction.
However, it is important to select antidepressants
depending on the individual patient symptoms
and characteristics.
As a general rule, polypharmacy should be
avoided and older people may need more frequent
monitoring and slower dose titration than their

References
1. Beekman AT, Copeland JR, Prince
MJ. Review of community prevalence
of depression in late life. Br. J
Psychiatry 1999; 174: 30711
2. World Health Organization. The
ICD-10 Classification of Mental
and Behavioural Disorders: clinical
descriptions and diagnostic
guidelines. Geneva: World Health
Organization, 1992
3. American Psychiatric Association.
Diagnostic and Statistical Manual
of Mental Disorders: DSM-IV, 4th
edn. Washington, DC: American
Psychiatric Association, 1994
4. David A. Depression and the
elderly. In: Dawson A, Tylee A, eds.
Depression: social and economic
timebomb. 1st edition pp 4954 BMJ
Books, 2001
5. Baldwin R, Wild R. Management of
depression in later life. Advances
in Psychiatric Treatment 2004; 10:
13139
6. Fernandez F. Depression and its
treatment in cardiac patients. Texas
Heart Institute Journal 1993; 20:
18897
7. Glassman A, OConnor C, Califf
R. Sertraline treatment of major
depression in patients with acute
MI or unstable angina. Journal of
American Medical Association 2002;
288: 7019
8. Sloan RW. Principles of drug therapy
in geriatric patients. Am. Fam.
Physician. 1992; 6: 270918
9. National Institute of Health and
Clinical Excellence (NICE). Clinical
Guideline 23. The management of
depression in primary and secondary
care. Dec. 2004
10. Giron M, Fastbom J, Winbald B.
Clinical Trials of antidepressants:
to what extent are the elderly
represented: a review. Int. J Geriatr
Psychiatry 2005; 3: 2017
11. British Medical Association.
Clinical Evidence. BMJ Publishing
Group Limited. www.nelh.nhs.uk/
clinicalevidence
12. Alexopoulos G, Katz I, Reynolds C,
et al. Pharmacotherapy of depressive
disorders in older patients. A post
graduate medicine special report.
Expert Consensus Guideline Series.
White Plains, NY
13. De Abajo FJ, Rodriguez LA, Montero
D. Association between selective
serotonin reuptake inhibitors and
upper gastrointestinal bleeding:
population based case-control study.
British Medical Journal 1999; 319:
11069
14. Wilson K, Mottram P, Sivanranthan A.
Antidepressants versus placebo for
depressed elderly. Cochrane Library
2001; 4
15. Kantona C, Livington G. How well do
antidepressants work in older people?
A systematic review of number
needed to treat. J of Affective Disord.
2002; 69: 4752
16. Taylor D, Paton C, Kerwin R.
The Maudsley-2003 Prescribing
Guidelines 7th Edition. MartinDunitz book
17. Baldwin R. Mood disorders in the
elderly. In Gelder M, Lopez-Ibor

J, Andreasen N. eds. New Oxford

Textbook of Psychiatry 1st edition part
8.5.4 Oxford University Press 2000
18. British Medical Association and
Royal Pharmaceutical Society
of Great Britain. British National
Formulary.BNF.org. March 2005
19. Committee on the Safety of
Medicines. Safety of selective
serotonin reuptake inhibitor
antidepressants. www.mhra.gov.uk/
news/2004/SSRIs_061204.pdf
20. IsbisterGK, Bowe SJ, Dawson A, et
al. Review of consecutive Selective
Serotonin Reuptake Inhibitors (SSRIs)
to a Toxicology unit. Journal of
Toxicology and Clinical Toxicology
2004; 42: 27785
21. Kelly CA, Dhaun N, Laing WJ, et al.
Comparative toxicity of citalopram
and newer antidepressants after
overdose. Journal of Toxicology and
Clinical Toxicology. 2004; 42: 6771
22. Niranjan K, Nasim A Hyponatraemia:
removing the risk in the elderly.
Geriatric Medicine 2005; 35: 1721
23. van Walraven C, Mamdani MM, Wells
PS, et al. Inhibition of serotonin
reuptake by antidepressants and
upper gastrointestinal bleeding in
elderly patients: retrospective cohort
study. British Medical Journal 2001;
323: 65558
24. Meijer W, Heerdink E, Nolen
W, et al. Association of risk of
abnormal bleeding with degree of
serotonin reuptake inhibition by
antidepressants. Arch Intern Med
2004; 164: 236770
25. Dalton S, Johansen C, Mellemkjeer L
et al. Use of SSRIs and risk of upper
gastrointestinal track bleeding: a
population based cohort study. Arch
Intern Med 2003; 163: 5964
26. Montgomery S, Baldwin D, Riley A.
Antidepressant medications: a review
of the evidence for drug induced
sexual dysfunction. Journal of
Affective Disorders 2002; 69: 11940
27. Hansen L. A critical review of
akathisia, and its possible association
with suicidal behaviour. Human
Psychopharmacology 2001; 16:
495505
28. Akagi H, Kumar M. Akathisia:
overlooked at a cost. British Medical
Journal 2002; 324: 15067
29. Bains J, Birks J, Dening T. The
efficacy of antidepressants in the
treatment of depression in dementia.
Cochrane Database Syst. Rev.
2002 (4) CD003944. Review PMD
12519625
30. Allain S, Schuck S, Mauduit N.
Depression in Parkinsons disease.
British Medical Journal 2000; 320:
12878
31. MacHale S. Managing depression
in physical illness. Advances in
psychiatric treatment 2002; 8:
297304
32. Thompson L, Coon D, GallagherThompson D, et al. Comparison
of desipramine and cognitive /
behavioural therapy in the treatment
of elderly outpatients with mild to
moderate depression. American
Journal of Geriatric Psychiatry 2001;
9: 22540

younger counterparts. There is also mounting

evidence to support the use of psychological
therapies such as cognitive behavioural therapy in
older people32 GM
Conflict of interest: none declared
february 2006 / midlife and beyond / geriatric medicine